tbuckley/cabot-search huggingface dataset:
Hepatic arterial infusion chemotherapy (HAIC) combined with tislelizumab and lenvatinib for advanced hepatocellular carcinoma (aHCC) with Vp3-4 portal vein tumor thrombosis (PVTT): A single-arm, phase II study.
Authors: Yongkang Xu, Shumin Fu, Ye Mao, Shenglan Huang, Dan Li, Jianbing Wu
Journal: Journal of Clinical Oncology (2023)

e16145 Background: aHCC patients (pts) with Vp3-4 PVTT have a poor prognosis. HAIC combined with immune checkpoint inhibitors and targeted therapies has shown local control and survival benefits in aHCC. However, the optimal combination in aHCC pts with Vp3-4 PVTT remains unclear. Here, we reported the preliminary efficacy and safety of HAIC combined with tislelizumab and lenvatinib in this population. Methods: In this ongoing, single-site, prospective, single-arm, phase II study, eligible pts were aged ≥18 years, histologically confirmed aHCC, ECOG PS ≤1, Child-Pugh A/B, and had at least 1 measurable lesion per RECIST 1.1. Pts received HAIC with modified FOLFOX (oxaliplatin, 85 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1; and 5-fluorouracil infusion 2400 mg/m 2 for 46 h), combined with lenvatinib (8 or 12 mg QD for body weight &lt;60 or ≥60 kg) and tislelizumab (200mg Q3W). HAIC was conducted repeatedly on demand. The primary endpoint was the objective response rate (ORR) per RECIST 1.1. Secondary endpoints included the ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: From June 2021 to January 2023, 27 aHCC pts with Vp3-4 PVTT were enrolled; of these, 22 pts were valuable for efficacy and safety analyses. The 22 pts were characterized with a median age of 52.5 years (range 33-72), 40.9% ECOG PS 0, 90.9%Child-Pugh A, and 45.5% extrahepatic metastasis. Till data cut-off (January 20, 2023), median follow-up was 11.3 months (95% CI, 6.0-13.1), 17 pts were alive and 14 pts remained on treatment. The ORR was 45.5% (95% CI, 25.1%-67.3%) with all partial responses per RECIST 1.1. Notably, 17 of 22 pts (77.3%; 95% CI, 54.2%-91.3%) achieved objective response as per mRECIST, with 6 (27.3%) complete responses and 11 (50%) partial responses. The DCR was 90.9% (95% CI, 69.4%-98.4%) either by RECIST 1.1 or mRECIST. Surgical conversion was achieved in 22.7% (5/22; 95% CI, 8.7%-45.8%) pts. Median PFS was not reached, with a 6- and 12-month PFS rate of 50% and 27.3%. OS data was not mature by the cut-off date. TRAEs were reported in 18 of 22 pts (81.8%). Most common TRAEs of any grade were hypertension (11/22, 50%), neutropenia (10/22, 45.5%), and aspartate aminotransferase (AST) increased (7/22, 31.8%). Grades ≥3 TRAEs occurred in 6 pts (27.3%), including 3 neutropenia (13.6%), 2 abdominal pain (9.1%), and 1 AST increased (4.6%). Conclusions: HAIC combined with tislelizumab and lenvatinib showed encouraging clinical activity and acceptable toxicity in aHCC pts with Vp3-4 PVTT, suggesting that this combination could be considered in this population. Study enrollment is ongoing, more mature data will be presented later. Clinical trial information: ChiCTR2200064384 .
Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric adenocarcinoma (FRUTINEOGA): A multicenter, phase II study.
Authors: Liucheng Wu, Yuzhou Qin, Mingwei Huang, Di Long
Journal: Journal of Clinical Oncology (2023)

e16063 Background: Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients (pts) with locally advanced GC, and SOX is the most common neoadjuvant regimen in China. Fruquintinib is a VEGFR inhibitor that blocks new blood vessel growth associated with tumor proliferation. It is a potent, highly selective small-molecule inhibitor of VEGFR-1,-2, and -3. The generally good tolerability in pts and fruquintinib’s low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. We aimed to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC. Methods: It was a prospective, multicenter, phase II study in pts with stage III (cT3/4aN+M0) GC. Pts received 2 to 4 cycles of fruquintinib (5mg qd D1-14, Q3W) plus SOX (oxaliplatin 130mg/m 2 D1, S-1 40-60mg bid D1-14 depending on body surface area (BSA), Q3W). Pts underwent D2 gastrectomy after neoadjuvant treatment. The primary endpoint was pathological response rate (pRR), and the secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), major pathological response rate (MPR), and R0 resection rate. Results: Up to February 3, 2023, 19 pts were eligible for the study. Median age was 62 years (29-73), 68.4% were male, and 21.1% were ECOG 1. Seven pts dropped out of clinical trial for AEs (2 pts), violation of treatment protocol (1 pt), staging error (2 pts), and refusal of surgery (2 pts). Twelve pts underwent surgery, 1 patient was found with peritoneal implantation, 11 patients underwent gastrectomy. Among the 11 pts, 9 pts achieved pRR (81.8%) and 3 pts achieved MPR (27.3%). The pathologic CR rate was 27.3% (3 of 11 pts). Moreover, 11 pts had curative intended operations and R0 resection rate was 90.9%. Among all the 19 pts, 16 pts received at least one dose of the combination treatment. A total of 2 pts had target lesions, 1 patient had complete response and 1 had partial response. Among the other 14 pts without target lesions, 1 (7.1%) had progressive disease with peritoneal implantation metastasis, and none had complete response. Furthermore, the most common TEAEs of grade ≥ 3 occurred in 19 pts were decreased appetite (21.1%), hypertension (21.1%), nausea (15.8%), vomiting (10.5%), oral mucositis (10.5%), fatigue (5.3%), diarrhea (5.3%) and respiratory infections (5.3%). There were neither new safety signals nor AEs inducing treatment deaths. Conclusions: The combination of fruquintinib and SOX as neoadjuvant treatment in patients with locally advanced GC is safe. The combination demonstrates promising evidence of anti-tumor efficacy in terms of pathological response. Clinical trial information: NCT05122091 .
Effects of oncolytic bacteria, SGN1, against a broad spectrum of malignancies in pre-clinical and clinical studies.
Authors: Allan Zijian Zhao, Fanghong Li, Jialuo Mai, Sujin Zhou, Yunhao Lai, Mengmeng Lu, Jincai Liang
Journal: Journal of Clinical Oncology (2023)

e15184 Background: It has been widely reported over the past 40 years that almost all human cancer cells examined are strongly dependent on methionine for growth and metastasis, largely owing to the deficiency of cancer cells in methionine salvage pathway. To specifically deprive cancer tissues of methionine without affecting systemic methionine content, we have developed the first oncolytic bacteria drug, SGN1, that is based on the attenuated Salmonella typhimurium and its tumor targeting ability, and overexpresses an L-methioninase gene. Currently, SGN1 has been approved for, and entered, clinical trials in the US and Taiwan, China (NCT05103345 &amp; NCT05038150). Methods: Cellular and animal models were used for examining the tumor-targeting effects and safety profiles of SGN1. We calculated the role of engineered Salmonella in cancer cells by RNA-seq analysis. Results: In preclinical cellular and xenograft models, SGN1 specifically targeted solid tumors， induced a sharp regression of several very divergent models of human carcinomas, caused a significant decrease of tumor cell invasion, and essentially eliminated the growth and metastasis of the xenograft tumors. RNA-Seq analysis revealed that the engineered Salmonella reduced the expression of a series of genes promoting cell growth, cell migration and invasion. Like the original attenuated Salmonella typhimurium (VNP20009), SGN1 has displayed excellent safety profiles based on the GLP-evaluation in multiple animal models. In preclinical human tumor-derived models, SGN1 exhibited strong inhibitory effects on tumor growth and metastasis in a broad spectrum of tumors, including, but not limited to, small cell lung carcinoma, osteosarcoma, hepatocellular cancer, breast cancer (including triple negative breast cancer), pancreatic cancer, prostate cancer, and cervical cancer. In investigator-initiated trial (IIT) studies, SGN1 significantly shrank, or completely lysed, patients’ tumor and ameliorated cachexia, while patients showed no severe adverse reaction except some transient fever and nausea. Conclusions: The first-in-class oncolytic bacteria, SGN1, featured with the ability of tumor-targeting and methionine hydrolysis, exhibits broad-spectrum antitumor activity and great potential for cancer therapy. Clinical trial information: NCT05038150 . Clinical trial information: NCT05103345 .
Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentomic patterns for multi-cancer early detection.
Authors: Su Yeon Kim, Seongmun Jeong, Wookjae Lee, Yujin Jeon, Yong-Jin Kim, Seowoo Park, Dayoung Go, Sanghoo Lee, Hyun Goo Woo, Jung-Ki Yoon, Young Sik Park, Young Tae Kim, Se-Hoon Lee, Kwang Hyun Kim, Yoojoo Lim, Sang-Hyun Song, Jin-Soo Kim, Hwang-Phill Kim, Duhee Bang, Tae-You Kim
Journal: Journal of Clinical Oncology (2023)

e15040 Background: The use of cfDNA sequencing has demonstrated great potential for cancer screening; particularly, methylation signatures, copy number variations, and fragmentomic profiles have proven to be effective for identifying early cancer signals. However, most large-scale studies have only focused on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform for multi-cancer early detection that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Methods: For a total of 950 plasma samples (361 healthy controls and 107 colon, 113 liver, 238 lung, and 131 prostate cancer) and 239 tissue samples, whole-genome methylation sequencing data were generated. Machine learning was conducted for multiple feature types engineered from cfDNA samples, and independent test performance was assessed. Results: A multi-feature cancer signature ensemble (CSE) classifier, integrating all features, outperformed single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models were 77.2% [CI 72-82], 61.4% [CI 56-67], and 60.5% [CI 55-66], respectively; but it was significantly increased to 87.7% [CI 84-91] with CSE ( p-value &lt; 0.0001). For tracing the tissue of origin, CSE enhanced the accuracy beyond the methylation classifier, from 74.7% [CI 69-80] to 77.5% [CI 72-82]. Conclusions: This work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.
Clinical analysis of immunotherapy rechallenge in advanced gastric cancer.
Authors: Xinxin Zhang, Xinfang Hou
Journal: Journal of Clinical Oncology (2023)

e16049 Background: To evaluate the efficacy and influencing factors of programmed cell death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with PD-1 monoclonal antibody rechallenge in the Department of Gastroenterology, Henan Cancer Hospital from January 2020 to December 2021 were retrospectively collected. Results: A total of 60 patients with PD-1 monoclonal antibody rechallenge therapy were collected; the median follow-up time was 12.2 months. The median progression-free survival (PFS 2 ) of PD-1 monoclonal antibody rechallenge therapy was 2.9 months, and the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS 2 of the same PD-1 monoclonal antibody for the first and second versus different PD-1 monoclonal antibody rechallenge treatment was (3.5 months vs. 1.9 months, P=0.006). The median PFS 2 of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS 2 was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS 1 ≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with PD-1 monoclonal antibody rechallenge with median PFS 2 ( P=0.034, HR=2.327, 95%CI 1.066-5.082). The incidence of adverse reactions in grade 1-2 and grade 3-4 of PD-1 monoclonal antibody rechallenge therapy was 83.3%, and 35.0%, respectively. and the safety was controllable. Conclusions: Rechallenge therapy with PD-1 monoclonal antibody is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.
TQB2450 plus anlotinib combined with paclitaxel and cisplatin as first-line treatment of advanced esophageal squamous cell carcinoma (ESCC): Update results of a single-arm, multicenter phase Ⅱ trial.
Authors: Junsheng Wang, Ning Li, Yanzhen Guo, Yufeng Cheng, Baosheng Li, Su-xia Luo
Journal: Journal of Clinical Oncology (2023)

e16034 Background: PD-1 inhibitors plus chemotherapy are the standard regimens of first-line treatment in advanced ESCC. Anlotinib, a multi-target TKI effectively inhibiting angiogenesis and improving tumor microenvironment, had been demonstrated to have promising efficacy and tolerable toxicity whether combined with chemotherapy as first-line treatment or monotherapy as second-line in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We have conducted a phase II trial to evaluate the efficacy and safety of anlotinib combined with TQB2450, cisplatin and paclitaxel as first-line therapy in advanced ESCC. Here is the update results with more enrolled patients and longer follow-up period. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg/m 2 , iv, d1, q3w) and cisplatin (60~75mg/m 2 , iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: From September 2021 to August 2022, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39/50, 78%) and ECOG PS 1 (39/50, 78%). At the data cutoff date of January 16, 2023, 45 pts were tumor response evaluable, among whom, 3 pts achieved complete response, 34 had partial response and 8 had stable disease. The ORR was 82.2% (95% CI: 68.0%, 92.0%) and the DCR was 100.0% (95% CI: 92.1%, 100.0%). Median PFS was not reached. The incidence of grade 3-4 treatment emergent adverse events (TEAEs) was 66% (33/50), mainly included neutropenia (34%, 17/50), leukopenia (20%, 10/50) and hypertension (20%, 10/50), platelet count decreased (6%, 3/50). There was no grade 5 TRAE. 17 pts (34%, 17/50) occurred treatment related serious AEs. Conclusions: TQB2450 plus anlotinib combined with paclitaxel and cisplatin showed significant efficacy and manageable safety profile as first-line treatment in advanced ESCC, which might provide a new treatment strategy for ESCC patients. Clinical trial information: NCT05013697 .
Predicting the immunotherapy response based on molecular subtypes of pan-immune signatures in gastrointestinal stromal tumor.
Authors: Ling Liu, Xiaohui Wang, Chan Dai, Zhihua Pei, Qiming Zhou, Dongliang Wang
Journal: Journal of Clinical Oncology (2023)

e23512 Background: Gastrointestinal stromal tumor (GIST) is the most common sarcoma, often originate in the stomach or the small intestine. Although the application of imatinib has brought a breakthrough in the clinical treatment of GIST, not all GIST patients are effective, and most GIST patients who receive imatinib sensitivity will develop drug resistance and eventually malignant progression. The tumor microenvironment (TME) is a key mediator of cancer progression and treatment outcome, and plays an important role in predicting cancer prognosis and treatment response. This study aims to investigate the role of TME in the treatment of GIST and the response to immunotherapy. Methods: Raw microarray data of 199 GIST patients were downloaded from GEO, including 159 KIT-mutant, 21 PDGFRA-mutant and 19 WT. All affymetrix datasets were re-normalized using the gcRMA package with default parameters. We integrated 275 TME and malignant signaling pathways related signatures from different database and previous researches, including CIBERSORT, MCP-counter, TIMER, and others. Fisher exact test's was used to identify signatures that differential between KIT-mutant, PDGFRA-mutant, and WT (p &lt; 0.05), and 85 signatures were finally obtained. To classify the molecular profiles, the expression patterns were assessed in all 199 GIST patients using unsupervised clustering based on their ssGSEA scores, and can be clustered into three distinct microenvironments. Results: Using GSEA with all TME signatures genes ranked by the log2(fold change) between the threee clustes, we found that gene sets were considered immune favorable in cluster A, including gene sets related to activated CD8+ T cells (p = 0.0003)and activated CD4 T cell signaling pathway (p = 0.009). Cluster B enriched to the epithelial mesenchymal transformation pathway (p = 0.04) and TGFb signaling pathway (p = 0.003), cluster C enriched into DNA-repair pathway (p = 0.02). In an independent skin cutaneous melanoma cohorts (n = 86) treated with anti-PD-1 therapy, patients were classified into three molecular clusters, which significantly corrleated with response to ipilimumab (p = 0.007). The percentage of responders to anti-PD-1 therapy in cluster A was 75% in contrast to only 10% in cluster B. The three molecular clusters discern a potential responder versus non-responder (AUC = 0.87; p = 0.0015), with essentially a 80% chance of correctly predicting the response, which supporting the utilization of the classification method. Conclusions: In this study, the immuno-infiltrating landscape was characterized based on pan-immune signatures using transcriptomic profile in GIST. The molecular subtypes derived from pan-immune signatures have the potential to predict the efficacy of immunotherapy.
Associating patient perceptions to poor uptake of aspirin (ASA) chemoprevention in a single-center cohort of patients with Lynch syndrome (LS).
Authors: Sachi Singhal, Yana Chertok, Emma D Riggs, Mary Beryl Daly, Dong Kim, Michael J. Hall
Journal: Journal of Clinical Oncology (2023)

e15662 Background: LS is among the most common hereditary cancer (CA) syndromes, underlying 3% cases of colorectal CA (CRC) and 8% of CRC &lt; 50 yrs. Pts with LS have a very high lifetime risk of CRC, which has been shown to be decreased by intensive colonoscopy (COLO) surveillance. However, interval LS CRCs can still develop, and adjunctive therapies like ASA have been recognized for their chemoprev benefits, with 35% risk reduction associated with sustained ( &gt; 2 yrs) use. Existing data are scarce on uptake of ASA chemoprev in LS pts, as well as pt-level factors that may impact uptake. Methods: PREVENTLynch recruited LS participants in the Fox Chase Cancer Center (FCCC) Risk Registry, who were invited to complete a one-time e-survey after providing informed consent (1/2020-6/2020; IRB 20-8014). Demographic/personal/familial CA history were collected. Inconvenience (INC), side effects (SEs), prevention reassurance (PR), and likelihood of recommending (LoR) available and emerging CA prevention modalities were measured on 9-point scales (low = 1 vs high = 9). Results: 116 LS pts completed the survey. Mean age was 53 yrs [range 23-76 ]. 24.7% (33/116) reported being on ASA, with 24.2% (8/33) taking it for an unrelated cardiac indication. 96.6% (112/116) had completed COLO, with 60.5% getting annual screening and 39.5% getting screening in 2-3 yrs. No significant difference was noted among ASA users and non-users based on age, race and underlying genetic LS subtype. A majority of pts (61.6%) were on ASA 81 mg/day, while 24.3% and 12% reported taking 325 and 650 mg/day, respectively. LS pts both taking and not taking ASA perceived it to be convenient (mean INC: 1.18 ASA users vs 2.11 non-users, p = 0.01). Concern for SEs was lower in ASA users than non-users (mean 1.09 vs 2.30, p = 0.003) while PR of the protective benefits was higher in the ASA users (mean PR 5.94 vs 3.23, p &lt; 0.001). When comparing ASA to COLO, COLO was seen as more INC than ASA by both ASA users and non-users (mean COLO INC 3.0 and 3.1, p = 0.0001 and 0.017 compared to ASA INC, respectively). ASA users were more likely to recommend ASA to others (8.13 vs 4.09, p &lt; 0.001). Conclusions: ASA uptake is low among LS pts. ASA is perceived as a favorable modality of chemoprev in only a fraction of LS pts, with perceived SEs and low PR as barriers to uptake. There is a critical need to address negative perceptions of chemoprev in LS patients as more options are developed. [Table: see text]
Occult lymph node metastasis in cN0 tongue squamous cell carcinoma: A prospective observational study.
Authors: Sanqian Huang, Feiping Li, Sunbin Wang, Zheng Wu, Yiting Li, Yujuan Zhou, Wenxiao Huang, Hui Wang, Yaqian Han, Hailin Zhang
Journal: Journal of Clinical Oncology (2023)

e18066 Background: Tongue squamous cell carcinoma (TSCC) is prone to occult lymph node metastasis, and preoperative evaluation of cervical nodes is critical for determining treatment strategies. There is scarce report of detecting occult lymph node metastasis in TSCC by using multi-parameter magnetic resonance imaging (mpMRI), spectral computed tomography (spectral CT) or other diagnostic functional imaging. In this study, we aimed to analyze the incidence and risk factors of occult lymph node metastasis in cN0 TSCC by comparing preoperative imaging with postoperative pathology results. Methods: This study prospectively enrolled newly-diagnosed cN0 TSCC patients admitted to the Hunan Cancer Hospital between May, 2022 and December, 2022. All patients underwent primary resection and selective dissection of cervical lymph nodes. MpMRI and spectral CT scan of oral cavity and neck were performed prior to surgery. Preoperative evaluation of lymph node metastasis was conducted by two senior radiologist independently. The location of cervical lymph nodes was assigned based on the 2013 consensus guidelines. Results: A total of 26 cN0 TSCC patients (6 cT1 stage, 13 cT2 stage, and 7 cT3 stage) were enrolled. The median age was 53 (range, 36-64), and there were 25 males. Among all patients, 13 patients underwent unilateral cervical lymph node dissection, while 13 patients underwent bilateral cervical lymph node dissection. A total of 208 lymphatic drainage areas were resected, and 1003 lymph nodes were removed. There were 7 of pT1, 12 of pT2, 7 of pT3 based on postoperative pathological stages. Besides, there are 21 cases staged pN0, 2 cases staged pN1, 2 cases staged pN2, and 1 case staged pN3. Among the 26 patients, 5 (19.23%) cases had occult lymph node metastasis. A total of 8 metastatic lymph nodes (4 in ipsilateral Ib level, 1 in contralateral Ib level, 3 in IIa level ipsilateral side) were detected in the whole group. No lymph node metastasis was detected in level IIb, III and IV. The median maximum diameter of metastatic lymph nodes was 12 mm (range 5 to 15 mm), and 1 extra-nodal extension was observed. Moreover, all occult lymph node metastases occurred in patients with a primary invasion depth of ≥ 5 mm (29.41%, 5/17). Conclusions: The incidence of occult lymph node metastasis in cN0 TSCC remains high under functional imaging diagnostic technology. Preventive neck dissection is necessary for patients with cN0 disease, especially those with primary tumor invasion depth exceeding 5 mm.